382
P. Thanigaimalai et al. / European Journal of Medicinal Chemistry 68 (2013) 372e384
41.9, 41.6, 40.0, 34.0, 28.8, 26.0, 23.4, 22.1; HRMS (ESI): m/z calcd for
C
5.85e5.68 (m, 1H), 4.93e4.80 (m, 1H), 3.87 (s, 3H), 3.39e3.13 (m,
2H), 2.70e2.55 (m, 1H), 2.54e2.40 (m, 1H), 2.39e2.29 (m, 1H),
2.28e2.04 (m, 2H), 2.03e1.92 (m, 1H), 1.90e1.66 (m, 3H), 0.96e0.80
25H30N5O4S [M þ H]þ 496. 2019 found 496. 2011.
4.8.3. N-((S)-1-(((S)-1-(Benzo[d]thiazol-2-yl)-1-oxo-3-((S)-2-
oxopyrrolidin-3-yl)propan-2-yl)amino)-4-methyl-1-oxopentan-2-
yl)-1H-indole-2-carboxamide (5c)
(m, 6H); 13C NMR (400 MHz, CD3OD):
d 193.4, 181.5, 175.6, 165.2,
164.1, 159.6, 155.9, 139.4, 138.9, 130.5, 129.2, 128.4, 126.4, 123.6 (2
carbons), 123.2, 112.7, 105.8, 94.8, 55.8, 55.7, 53.3, 41.8, 41.5, 40.0,
34.0, 28.8, 26.0, 23.3, 22.1; HRMS (ESI): m/z calcd for C30H34N5O5S
[M þ H]þ 576.2281 found 576.2268.
Yield 51%; light yellow solid; 1H NMR (400 MHz, CD3OD):
d
8.10e8.06 (m, 2H), 7.63e7.54 (m, 3H), 7.47e7.38 (m, 1H), 7.23e
7.15 (m, 2H), 7.14e7.04 (m, 1H), 5.70e5.67 (m, 1H), 4.75e4.68 (m,
1H), 3.49e3.29 (m, 2H), 2.78e2.62 (m, 1H), 2.61e2.41 (m, 1H),
2.39e2.24 (m, 1H), 2.23e2.03 (m, 2H), 2.02e1.72 (m, 3H), 0.98e
4.8.8. N-((S)-1-(((S)-1-(Benzo[d]thiazol-2-yl)-1-oxo-3-((S)-2-
oxopyrrolidin-3-yl)propan-2-yl)amino)-4-methyl-1-oxopentan-2-
yl)-4-methoxy-1H-indole-2-carboxamide (5h)
0.88 (m, 6H); 13C NMR (400 MHz, CD3OD):
d 193.4, 181.8, 175.4,
165.4, 164.0, 154.7, 138.2, 131.6, 129.2, 128.9, 128.4, 126.4, 125.2,
123.6, 122.2, 121.2, 113.0, 105.3, 55.7, 53.4, 41.8, 41.5, 40.0, 33.9, 28.8,
26.0, 23.3, 22.1; HRMS (ESI): m/z calcd for C29H32N5O4S [M þ H]þ
546.2175 found 546.2157.
Yield 45%; light yellow solid; 1H NMR (400 MHz, CDCl3):
d 9.65
(br s, 1H), 8.89 (br s, 1H), 8.57 (br s, 1H), 8.08e8.06 (m, 1H), 7.98e
7.94 (m, 1H), 7.56e7.49 (m, 2H), 7.25e6.81 (m, 4H), 6.75e6.43 (m,
1H), 5.99e5.60 (m, 1H), 5.00e4.80 (m, 1H), 3.92 (s, 3H), 3.45e3.10
(m, 2H), 2.98e1.64 (m, 8H), 0.99e0.83 (m, 6H); 13C NMR (400 MHz,
4.8.4. N-((S)-1-(((S)-1-(Benzo[d]thiazol-2-yl)-1-oxo-3-((S)-2-
oxopyrrolidin-3-yl)propan-2-yl)amino)-4-methyl-1-oxopentan-2-
yl)-5-methoxy-1H-indole-2-carboxamide (5d)
CD3OD): d 193.4, 181.7, 175.3, 165.4, 164.0, 154.7, 152.8, 140.3, 138.2,
130.1, 129.2, 128.4, 126.49, 126.43, 123.6, 119.6, 104.8, 104.5, 103.7,
55.7, 53.4, 41.8, 41.5, 40.0, 34.0, 30.6, 28.8, 26.0, 23.3, 22.1; HRMS
(ESI): m/z calcd for C30H34N5O5S [M þ H]þ 576.2281 found
576.2264.
Yield 46%; light yellow solid; 1H NMR (400 MHz, CDCl3):
d 8.10e
8.06 (m, 1H), 8.00e7.96 (m, 1H), 7.56e7.48 (m, 2H), 7.07e7.00 (m,
2H), 6.96e6.92 (m, 2H), 5.82e5.68 (m, 1H), 4.80e4.75 (m, 1H), 3.85
(s, 3H), 3.44e3.26 (m, 2H), 2.70e2.42 (m, 2H), 2.41e2.14 (m, 1H),
2.13e1.90 (m, 2H), 1.89e1.64 (m, 3H), 0.98e0.88 (m, 6H); 13C NMR
4.8.9. N-((S)-1-(((S)-1-(Benzo[d]thiazol-2-yl)-1-oxo-3-((S)-2-
oxopyrrolidin-3-yl)propan-2-yl)amino)-4-methyl-1-oxopentan-2-
yl)-4-isopropoxy-1H-indole-2-carboxamide (5i)
(400 MHz, CD3OD):
d 193.5, 181.8, 175.4, 165.6, 164.0, 155.8, 154.7,
138.3, 133.8, 132.0, 129.2, 128.3, 127.1, 126.4, 123.6, 116.7, 113.9,
105.2, 103.2, 56.2, 55.7, 53.4, 41.5, 40.0, 33.9, 29.3, 28.8, 26.1, 23.4,
22.0; HRMS (ESI): m/z calcd for C30H34N5O5S [M þ H]þ 576.2281
found 576.2294.
Yield 49%; light yellow solid; 1H NMR (400 MHz, CD3OD):
d
8.07e8.01 (m, 2H), 7.56e7.44 (m, 2H), 7.34e7.25 (m, 1H), 7.20e
7.09 (m, 1H), 7.07e6.95 (m, 1H), 6.60e6.48 (m, 1H), 5.72e5.62 (m,
1H), 4.78e4.60 (m, 2H), 3.40e3.18 (m, 2H), 2.80e2.65 (m, 1H),
2.64e2.40 (m, 1H), 2.39e2.20 (m, 1H), 2.19e2.00 (m, 2H), 1.99e1.62
(m, 3H), 1.40e1.27 (m, 6H), 0.99e0.83 (m, 6H); 13C NMR (400 MHz,
4.8.5. N-((S)-1-(((S)-1-(Benzo[d]thiazol-2-yl)-1-oxo-3-((S)-2-
oxopyrrolidin-3-yl)propan-2-yl)amino)-4-methyl-1-oxopentan-2-
yl)-5-hydroxy-1H-indole-2-carboxamide (5e)
CD3OD):
d 193.4, 181.8, 175.4, 165.4, 164.0, 154.6, 153.7, 140.1, 138.2,
130.2, 129.2, 128.3, 126.4, 126.2, 123.6, 121.3, 106.0, 103.36, 103.32,
71.1, 55.7, 53.4, 41.8, 41.5, 40.0, 34.0, 28.7, 26.0, 23.4, 22.5 (2 car-
bons), 22.1; HRMS (ESI): m/z calcd for C32H38N5O5S [M þ H]þ
604.2594 found 604.2603.
Yield 37%; light yellow solid; 1H NMR (400 MHz, CD3OD):
d
8.08e8.04 (m, 2H), 7.57e7.50 (m, 2H), 7.30e7.23 (m, 1H), 7.02e
6.93 (m, 2H), 6.81 (dd, J ¼ 8.9, 2.3 Hz, 1H), 5.70e5.65 (m, 1H), 4.75e
4.65 (m, 1H), 3.40e3.21 (m, 2H merged with CD3OD), 2.80e2.60 (m,
1H), 2.59e2.40 (m,1H), 2.39e2.22 (m,1H), 2.21e1.93 (m, 2H),1.92e
1.62 (m, 3H), 1.00e0.90 (m, 6H); 13C NMR (400 MHz, CD3OD):
4.8.10. N-((S)-1-(((S)-1-(Benzo[d]thiazol-2-yl)-1-oxo-3-((S)-2-
oxopyrrolidin-3-yl)propan-2-yl)amino)-4-methyl-1-oxopentan-2-
yl)-4-isobutoxy-1H-indole-2-carboxamide (5j)
d
193.4, 175.4, 165.6, 165.4, 164.0, 154.7, 152.3, 138.2, 133.5, 132.7,
129.6, 128.4, 128.3, 126.5, 123.6, 116.2, 113.6, 105.8, 104.6, 55.7, 53.4,
Yield 52%; light yellow solid; 1H NMR (400 MHz, CD3OD):
41.8, 41.6, 40.0, 34.0, 28.8, 26.1, 23.3, 22.1; HRMS (ESI): m/z calcd for
C
d 8.04e8.00 (m, 2H), 7.52e7.44 (m, 2H), 7.35e7.20 (m, 1H), 7.10 (t,
29H32N5O5S [M þ H]þ 562.2124 found 562.2133.
J ¼ 8.0 Hz, 1H), 7.01e6.97 (m, 1H), 6.50e6.42 (m, 1H), 5.75e5.65 (m,
1H), 4.75e4.65 (m, 1H), 3.87e3.82 (m, 2H), 3.40e3.20 (m, 2H),
2.76e2.47 (m, 1H), 2.45e2.28 (m, 2H), 2.27e2.15 (m, 1H), 2.14e2.00
(m, 2H), 1.99e1.65 (m, 3H), 1.09e1.06 (m, 6H), 0.99e0.83 (m, 6H);
4.8.6. N-((S)-1-(((S)-1-(Benzo[d]thiazol-2-yl)-1-oxo-3-((S)-2-
oxopyrrolidin-3-yl)propan-2-yl)amino)-4-methyl-1-oxopentan-2-
yl)-5-chloro-1H-indole-2-carboxamide (5f)
13C NMR (400 MHz, CD3OD):
d 193.4,181.8, 175.5,165.4,164.0,155.1,
Yield 41%; white solid; 1H NMR (400 MHz, CD3OD):
d
8.00e7.93
154.6, 139.8, 138.2, 130.1, 129.2, 128.3, 126.4, 126.3, 123.6, 120.3,
106.0, 103.1, 101.2, 75.3, 55.7, 53.4, 41.8, 41.5, 40.0, 34.1, 29.7, 28.7,
26.0, 23.4, 22.1, 19.7 (2 carbons); HRMS (ESI): m/z calcd for
(m, 2H), 7.50e7.40 (m, 3H), 7.28 (t, J ¼ 8.0 Hz, 1H), 7.06 (dd, J ¼ 8.8,
2.0 Hz, 1H), 7.05e6.97 (m, 1H), 5.62e5.56 (m, 1H), 4.65e4.55 (m,
1H), 3.30e3.12 (m, 2H merged with CD3OD), 2.70e2.62 (m, 1H),
2.52e2.30 (m, 2H), 2.29e2.13 (m, 1H), 2.11e1.83 (m, 2H), 1.82e1.55
C
33H40N5O5S [M þ H]þ 618.2750 found 618.2767.
(m, 2H), 0.90e0.80 (m, 6H); 13C NMR (400 MHz, CD3OD):
d
193.5,
4.8.11. N-((S)-1-(((S)-1-(Benzo[d]thiazol-2-yl)-1-oxo-3-((S)-2-
oxopyrrolidin-3-yl)propan-2-yl)amino)-4-methyl-1-oxopentan-2-
yl)-4-hydroxy-1H-indole-2-carboxamide (5k)
181.8, 175.3, 165.6, 163.5, 154.7, 138.3, 136.6, 133.2, 129.8, 128.4,
128.3, 126.7, 125.3, 123.6, 121.9, 114.4, 104.7, 104.6, 55.6, 53.4, 41.8,
41.5, 40.0, 33.9, 28.8, 26.0, 23.3, 22.1; HRMS (ESI): m/z calcd for
Yield 51%; white solid; 1H NMR (400 MHz, CD3OD):
d 8.00e
C
29H31ClN5O4S [M þ H]þ 580.1785 found 580.1795.
7.95 (m, 2H), 7.50e7.38 (m, 2H), 7.24e7.12 (m, 1H), 6.97e6.91 (m,
1H), 6.85e6.78 (m, 1H), 6.31 (d, J ¼ 7.6 Hz, 1H) 5.62e5.54 (m, 1H),
4.62e4.55 (m, 1H), 3.35e3.10 (m, 2H merged with CD3OD), 2.70e
2.53 (m, 1H), 2.51e2.21 (m, 2H), 2.20e2.12 (m, 2H), 2.10e1.83 (m,
1H), 1.82e1.58 (m, 3H), 0.90e0.82 (m, 6H); 13C NMR (400 MHz,
4.8.7. N-((S)-1-(((S)-1-(Benzo[d]thiazol-2-yl)-1-oxo-3-((S)-2-
oxopyrrolidin-3-yl)propan-2-yl)amino)-4-methyl-1-oxopentan-2-
yl)-6-methoxy-1H-indole-2-carboxamide (5g)
Yield 38%; white solid; 1H NMR (400 MHz, CDCl3):
d
8.97 (br d,
CD3OD): d 193.4, 181.8, 175.4, 165.4, 154.7, 152.8, 140.3, 138.2,
1H), 8.72 (br d,1H), 8.18e8.06 (m,1H), 8.00e7.92 (m,1H), 7.58e7.44
(m, 2H), 7.00e6.79 (m, 1H), 6.78e6.75 (m, 1H), 6.40e6.25 (m, 1H),
130.1, 129.2, 128.4, 126.5, 126.49, 126.43, 123.6, 119.6, 104.8, 104.5,
103.1, 55.7, 53.4, 41.8, 41.5, 40.0, 34.0, 28.8, 26.0, 23.3, 22.1; HRMS